The genome of poliovirus is a single-stranded molecule of messenger RNA polarity ("positive strand"), containing approximately 7500 nucleotides. Its 5' end is linked to a small peptide, VPg, and its 3' end is a stretch of poly(A) 40 to 100 nucleotides long. More than 800 noncoding nucleotides are located at the two ends of poliovirus RNA:742 at its 5' end and 65 preceding the poly(A) at its 3' end. An open reading fame initiated by an AUG at position 743 extends over 6528 nucleotides and encodes a polyprotein of about 250,000 daltons.
Unlike most eukaryotic mRNAs, picornaviral RNAs (e.g., poliovirus, encephalomyocarditis (EMC) virus) are not "capped" at their 5' end. Poliovirus terminates in pUp, instead of in the "capping" group m.sup.7 G(5')ppp(5')N . . . which is found on almost all other mRNAs. Recognition of the capped end of mRNA by one or more specific proteins has been shown to be important for gene expression. The cap structure appears to facilitate stable complex formation between 40S ribosomal subunits and mRNA during translation initiation. Sonenberg, N., Advances in Virus Research, 33:175-204 (1987). Poliovirus and other picornaviruses, however, translate their genomes in a cap-independent manner.
Infection of mammalian cells by a picornavirus is known to result in selective inhibition of host cell protein synthesis. In the case of poliovirus, selective inhibition occurs and translation of cellular mRNA steadily decreases as virus-specific translation increases. Within a short time (i.e., 2 to 3 hours) after infection, polioviral RNA is translated almost exclusively. Bernstein, H.D. et al, Molecular and Cellular Biology, 5:2913-2923 (1985).
The exact mechanism by which cap-dependent translation is inhibited in poliovirus-infected cells is still ill defined. However, it has been demonstrated that one of the poliovirus proteins, protein 2A, plays a critical role in this inhibition. One hypothesis as to the role of 2A is that, through the action of a cellular intermediate, it induces cleavage of eukaryotic initiation factor 4F, a component of the cap binding complex. The result is a decreased affinity of ribosomes for cellular mRNAs. It is thought that the poliovirus then takes advantage of the lack of competition by other mRNAs and translates its own genome with high efficiency.